Cancer as one of the major diseases is still the most common and is seriously threatening the health of human beings, becoming the second biggest health killer. Current means for treating cancers include methods such as surgical removal, radiotherapy, chemotherapy, immunotherapy, interventional therapy, iontophoresis and the like, or combinations thereof. Among all the methods, chemotherapy is the most widely used and has been used for various types of cancers especially those which cannot be treated with other methods. Although many compounds with chemotherapeutic effects have been used clinically, most chemotherapeutic methods are only to delay the deterioration of the cancer instead of a real cure because of the lack of a sufficiently outstanding efficacy and the narrow therapeutic ranges. Tumors and metastasis thereof which have developed resistance to certain drugs usually cannot be treated with chemotherapy, and some tumors are intrinsically resistant to certain types of chemotherapeutic drugs. The resistance of tumors against a chemotherapeutic drug is gradually developed during the treatment. Therefore, the effects of current chemotherapeutic drugs in treating different kinds of tumors are seriously limited. Furthermore, many chemotherapeutic drugs in different categories for cancer treatment generate very serious side effects so that the chemotherapy can hardly proceed. Thus, it is still urgently desired to find new anti-cancer drugs with better efficacy and fewer side effects in order to safeguard the health of human beings.
A variety of viruses such as hepatitis B virus, hepatitis C virus and human immunodeficiency virus and so on have brought severe damage to the human society. At the time of the outbreak of bird flu, there was almost no medicament for it. Among the 6 billion people in the entire world, half of them live the high prevalence areas of hepatitis B virus (HBV), about 2 billion have been confirmed being infected by HBV, 0.3-0.4 billion have chronic HBV infection, and 15%-25% of them eventually will die from liver cirrhosis and liver cancer. In the worldwide top 10 causes of death related to a disease, hepatitis B is No. 7, causing around 1 million deaths annually and making it an important disease threatening the health of human beings. There are many challenges present in the development of a HBV medicament, such as drug resistance, undetermined drug target and drug resistance development et al. Therefore, researches to develop new anti-HBV drugs with high efficacy and low toxicity are still desired.
Hepatitis C is becoming a global epidemic and is the foremost cause of end-stage liver disease in western countries and Japan. According to a statistics coming from WHO in 2009, there were around 180 million people globally having hepatitis C and there were around 35 thousand emerging hepatitis C cases annually. The global death caused by live diseases associated with hepatitis C almost doubles every 10 years. The current death rate of hepatitis C is ranked the tenth among all the diseases worldwide and there is no vaccine for it yet. A commonly recognized routine treatment for chronic hepatitis C uses ribavirin developed by an American, Valeant, and PEGylated interferon in combination. The sustained virological response (SVR) of HCV is only 47%-54%. And there are some patients who may be forced to stop taking the mediation because of severe side effects, and for many patients there is even no effective medicament available for them. Consequently, it is extremely urgent to develop new anti-HCV drugs with high efficacy and low toxicity.
Human immunodeficiency virus (HIV) is a major disease that is seriously threatening human health. Although several nucleoside based medicaments have been used to alleviate the suffering of people with AIDS, most of them has low efficacy and severe toxic side effects, and induces drug resistance very easily. Therefore, researches on new nucleoside-based anti-AIDS medicament are still recognized as an important field for humans to defeat serious diseases.
The monomeric nucleoside from natural products, deoxy nucleic acid (DNA) and ribose nucleic acid (RNA), can be modified to produce natural product medicament which would have lower toxic side effect. Although over 70 nucleoside-based medicaments have been widely used so far in the treatment for diseases such as cancer and viral disease, there remain unmet medical needs and better nucleoside-based drugs are still needed to be developed. The most desirable medicament should be against virus and tumor at the same time and would make an important contribution to human's well-being.